The chemically modified nucleotide, TrpdU (and its 2′-modified analogs), which bears a 3-(2-aminoethyl)-indole side chain, is useful, for example, in developing high-affinity aptamers to target analytes, such as proteins. The indole ring of TrpdU is electron-rich and polarizable, which may facilitate formation of secondary structure and complementary hydrophobic interfaces with target analytes. To date, TrpdU has not performed as well as other modified nucleotides as a phosphoramidite reagent in solid-phase oligonucleotide synthesis, and its use has therefore been limited.
There remains a need in the art for an improved TrpU phosphoramidite, and improved methods of making a TrpU phosphoramidite.